Plasma cytokine levels and risk of HIV type 1 (HIV-1) transmission and acquisition: a nested case-control study among HIV-1-serodiscordant couples

Abstract

Background: A heightened proinflammatory state has been hypothesized to enhance human immunodeficiency virus type 1 (HIV-1) transmission - both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.

Methods: Using prospective data from heterosexual African couples with HIV-1 serodiscordance, we conducted a nested case-control analysis to assess the relationship between cytokine concentrations and the risk of HIV-1 acquisition. Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was transmitted to the seronegative partner during the study; control couples (n = 321) were serodiscordant couples in which HIV-1 was not transmitted to the seronegative partner. Differences in a panel of 30 cytokines were measured using plasma specimens from both HIV-1-susceptible and HIV-1-infected partners. Plasma was collected before seroconversion for cases.

Results: For both HIV-1-infected and HIV-1-susceptible partners, cases and controls had significantly different mean responses in cytokine panels (P < .001, by the Hotelling T(2) test), suggesting a broadly different pattern of immune activation for couples in which HIV-1 was transmitted, compared with couples without transmission. Individually, log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly higher for both HIV-1-susceptible and HIV-1-infected case partners, compared with HIV-1-susceptible and HIV-1-infected control partners (P < .01 for all comparisons). In multivariate analysis, HIV-1 transmission was significantly associated with elevated CXCL10 concentrations in HIV-1-susceptible partners (P = .001) and with elevated IL-10 concentrations in HIV-1-infected partners (P = .02).

Conclusions: Immune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.

Keywords: Africa; HIV-1 acquisition; immune activation.

Figure 1.

Mean log₁₀ blood plasma concentrations for interleukin 10 (IL-10) and CXCL10 cytokines among cases and controls. The mean distribution of log₁₀ concentration for IL-10 and CXCL10 for human immunodeficiency virus type 1 (HIV-1)–susceptible case and control partners (A) and HIV-1–infected case and control partners (B). Individual log₁₀ cytokine concentrations plotted with mean (middle bar) and standard deviation (top and bottom bars).

Figure 2.

Correlation of interleukin 10 (IL-10) and CXCL10 log₁₀ blood plasma concentrations. Scatterplot and regression line with Spearman ρ and P values for IL-10 and CXCL10 log₁₀ concentrations in human immunodeficiency virus type 1 (HIV-1)–susceptible partners (A), IL-10 and CXCL10 log₁₀ concentrations in HIV-1–infected partners (B), IL-10 log₁₀ concentrations within serodiscordant couples (C), and CXCL10 log₁₀ concentrations within serodiscordant couples (D).